Discovery of RC-752, a Novel Sigma-1 Receptor Antagonist with Antinociceptive Activity: A Promising Tool for Fighting Neuropathic Pain.
antinociceptive activity
neuropathic pain
sigma 1 receptor antagonist
zebrafish model
Journal
Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453
Informations de publication
Date de publication:
05 Jul 2023
05 Jul 2023
Historique:
received:
30
05
2023
revised:
30
06
2023
accepted:
02
07
2023
medline:
29
7
2023
pubmed:
29
7
2023
entrez:
29
7
2023
Statut:
epublish
Résumé
Neuropathic pain (NP) is a chronic condition resulting from damaged pain-signaling pathways. It is a debilitating disorder that affects up to 10% of the world's population. Although opioid analgesics are effective in reducing pain, they present severe risks; so, there is a pressing need for non-opioid pain-relieving drugs. One potential alternative is represented by sigma-1 receptor (S1R) antagonists due to their promising analgesic effects. Here, we report the synthesis and biological evaluation of a series of S1R antagonists based on a 2-aryl-4-aminobutanol scaffold. After assessing affinity toward the S1R and selectivity over the sigma-2 receptor (S2R), we evaluated the agonist/antagonist profile of the compounds by investigating their effects on nerve growth factor-induced neurite outgrowth and aquaporin-mediated water permeability in the presence and absence of oxidative stress. (
Identifiants
pubmed: 37513874
pii: ph16070962
doi: 10.3390/ph16070962
pmc: PMC10386076
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : MUR- Ministero dell'Università e della Ricerca
ID : PON R&I 2014-2020-Asse IV "Istruzione e Ricerca per il recupero-REACT-EU", Azione IV.6 "Contratti di Ricerca su tematiche Green".
Références
Physiol Rev. 2021 Jan 1;101(1):259-301
pubmed: 32584191
Drug Metab Dispos. 2005 Sep;33(9):1304-11
pubmed: 15932954
Eur J Pharmacol. 2005 Mar 21;511(1):73-4
pubmed: 15777781
Trends Pharmacol Sci. 2019 Sep;40(9):636-654
pubmed: 31387763
PLoS One. 2012;7(5):e37989
pubmed: 22655093
Int J Mol Sci. 2021 Sep 10;22(18):
pubmed: 34575952
Int J Mol Sci. 2020 Nov 27;21(23):
pubmed: 33260926
Bioorg Med Chem. 2017 Jan 1;25(1):11-19
pubmed: 27838169
BMJ. 2020 Apr 28;369:m1315
pubmed: 32345589
Mol Imaging Biol. 2017 Oct;19(5):779-786
pubmed: 28280965
Lancet Neurol. 2010 Aug;9(8):807-19
pubmed: 20650402
J Med Chem. 2012 Oct 11;55(19):8211-24
pubmed: 22784008
Pain. 1992 Sep;50(3):355-363
pubmed: 1333581
Pharmacol Rev. 2018 Apr;70(2):315-347
pubmed: 29500312
Cochrane Database Syst Rev. 2017 May 22;5:CD011669
pubmed: 28530786
Eur Surg Res. 2015;55(1-2):43-57
pubmed: 25871531
Pain Res Manag. 2020 Jun 16;2020:7408508
pubmed: 32617124
Chem Res Toxicol. 2020 Jan 21;33(1):95-118
pubmed: 31625720
J Nucl Med. 2014 Jan;55(1):147-53
pubmed: 24337599
Cochrane Database Syst Rev. 2017 Jun 15;6:CD003726
pubmed: 28616956
Eur J Med Chem. 2018 Oct 5;158:353-370
pubmed: 30223122
Front Pharmacol. 2019 Jun 12;10:613
pubmed: 31263413
Cell Tissue Res. 2019 Jul;377(1):21-43
pubmed: 30778732
Birth Defects Res B Dev Reprod Toxicol. 2010 Feb;89(1):66-77
pubmed: 20166227
Int J Mol Sci. 2017 Dec 08;18(12):
pubmed: 29292793
Rev Neurol (Paris). 2019 Jan - Feb;175(1-2):16-25
pubmed: 30385075
Bioorg Med Chem. 2011 Nov 1;19(21):6210-24
pubmed: 21967807
J Med Chem. 2012 Oct 11;55(19):8272-8282
pubmed: 22853801
Pain Rep. 2021 Jan 27;6(1):e884
pubmed: 33537521
Pharm Res. 1993 Jul;10(7):1093-5
pubmed: 8378254
J Med Chem. 2021 Jan 14;64(1):890-904
pubmed: 33372782
Eur J Med Chem. 2016 Nov 29;124:649-665
pubmed: 27614411
Inflamm Res. 2015 Jun;64(6):377-81
pubmed: 25902777
Pain Rep. 2021 Jan 07;6(1):e885
pubmed: 33458558
Int J Mol Sci. 2020 Oct 18;21(20):
pubmed: 33081037
ACS Pharmacol Transl Sci. 2022 Mar 17;5(4):240-254
pubmed: 35434530
Biochem Pharmacol. 1994 Apr 29;47(9):1469-79
pubmed: 8185657
Sci Rep. 2017 Mar 03;7:42717
pubmed: 28256516
J Peripher Nerv Syst. 2019 Oct;24 Suppl 2:S6-S12
pubmed: 31647155
Front Chem. 2020 Jun 30;8:495
pubmed: 32695745
Antioxid Redox Signal. 2016 Jun 20;24(18):1031-44
pubmed: 26972385
Sci Rep. 2016 Nov 25;6:37835
pubmed: 27886264
J Pain Res. 2019 May 16;12:1537-1551
pubmed: 31190965
Future Med Chem. 2016;8(3):287-95
pubmed: 26898712
Int J Biochem Cell Biol. 2020 Sep;126:105803
pubmed: 32668330
Pharmacol Res. 2021 Jan;163:105339
pubmed: 33276102
Pain. 1977 Dec;4(2):161-174
pubmed: 564014
Front Pharmacol. 2019 Apr 24;10:419
pubmed: 31068816
Int J Mol Sci. 2022 Jan 06;23(2):
pubmed: 35054797
Transpl Int. 2018 Nov;31(11):1268-1278
pubmed: 29908082
Handb Exp Pharmacol. 2017;244:131-161
pubmed: 28275913
J Oncol. 2011;2011:201593
pubmed: 22203844
BMC Bioinformatics. 2008 Sep 24;9:396
pubmed: 18816385
Lab Anim Res. 2020 Dec 9;36(1):45
pubmed: 33298163
Molecules. 2021 Jun 19;26(12):
pubmed: 34205334
Mol Pain. 2014 Apr 16;10:26
pubmed: 24739328
J Pharmacol Exp Ther. 2002 Dec;303(3):1227-37
pubmed: 12438547
Neurotherapeutics. 2018 Jan;15(1):178-189
pubmed: 28924870
FASEB J. 2020 Apr;34(4):5951-5966
pubmed: 32157739
Front Pharmacol. 2019 May 31;10:519
pubmed: 31214020
Semin Neurol. 2016 Oct;36(5):462-468
pubmed: 27704502
Front Pharmacol. 2019 May 14;10:490
pubmed: 31156430
Eur J Pharmacol. 2010 Jan 25;626(2-3):250-5
pubmed: 19836387
Sci Rep. 2016 Apr 18;6:24591
pubmed: 27087602
J Pain. 2012 Nov;13(11):1107-21
pubmed: 23063344
Lancet Neurol. 2020 Sep;19(9):767-783
pubmed: 32622375
Pain Med. 2022 Apr 8;23(4):774-781
pubmed: 34931670
Lancet Neurol. 2015 Feb;14(2):162-73
pubmed: 25575710
Cent Nerv Syst Agents Med Chem. 2009 Sep;9(3):172-83
pubmed: 20021351
Crit Rev Oncol Hematol. 2012 Apr;82(1):51-77
pubmed: 21908200
Xenobiotica. 2001 Aug-Sep;31(8-9):591-8
pubmed: 11569527
Curr Med Res Opin. 2018 Apr;34(4):677-682
pubmed: 29023146
Pharm Pat Anal. 2020 May;9(3):77-85
pubmed: 32539668